The burden and care cascade in young and middle-aged patients with diabetes hypertension comorbidity with abdominal obesity in India: A nationally representative cross-sectional survey

We ascertained the burden, determinants, and care cascade in the young and middle-aged patients having co-existing hypertension (HTN), Diabetes Mellitus (DM), and abdominal obesity in India from a secondary data analysis of nationally representative data. The study examined cross-sectional data from the National Family Health Survey (NFHS-5) conducted in India from 2019 to 2021 in 788974 individuals aged 15–49 years including 695707 women and 93267 men. The weighted prevalence of DM-HTN comorbidity with high waist circumference in the sample was 0.75% (95% CI: 0.71 to 0.79) including 46.33% (95% CI: 44.06 to 48.62) newly diagnosed cases detected for HTN and high blood sugars. The weighted prevalence of Metabolic syndrome as per NCEP ATPIII criteria was found to be 1.13% (95% CI: 1.08 to 1.17). Only 46.16% existing cases were treated with both anti-diabetes and antihypertensive medication (full treatment), while 34.71% cases were untreated. On adjusted analysis, increasing age, females, higher wealth index, high fat diet, obesity and comorbidities were significantly associated with having DM-HTN comorbidity along with high-waist circumference. More than half of young and middle aged-population in India with DM-HTN-abdominal obesity triad are not initiated on treatment for DM and HTN comorbidities, while a majority of the previously diagnosed cases have uncontrolled blood pressure and poor glycemic control. The poor cascade of care for DM and HTN in these high-risk group of patients may substantially increase their risk for early progression and severity of microvascular and macrovascular complications especially cardiovascular disease.

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INTRODUCTION
The Global Action Plan for the Prevention and Control of Noncommunicable Diseases (NCDs), aims to halt by 2025 the increasing burden of diabetes mellitus (DM) and reduce the relative prevalence of hypertension (HTN) by 25% [1].NCDs account for 71% of the total global mortality and 15 million premature deaths before the age of 70 years, with the WHO setting the goal of reducing premature mortality from NCDs by onethird by 2030 [1,2].
The number of deaths from NCDs in India in 2017 was estimated to be around 4.7 million, accounting for 49% of all-cause mortality.The leading causes of these deaths were cardiovascular diseases (23%), chronic respiratory diseases (9%), cancer (6%) and diabetes (2.4%) with 65% of these deaths being premature and preventable [3].The estimated percentage of disability-adjusted life years (DALYs) in India attributable to NCDs has increased from 30% of all DALYs in 1990 to 58% in 2019 [4].
Leading risk factors driving the burden of cardiovascular diseases, the single biggest cause of mortality worldwide include diabetes mellitus (DM), hypertension (HTN), and obesity [5].As of 2021, 74 million individuals live in India with DM and this burden expected to reach 125 million by 2045 [6].Additionally, Hypertension, a major modifiable risk factor for cardiovascular disease (CVD), has an estimated prevalence in 24% of men and 21% of women as per a nationally representative cross-sectional survey in the 15-49 aged population of India [7,8].
Abdominal obesity is a condition of excessive fat deposition around the abdominal region signifying insulin resistance and ectopic fat accumulation with elevated adipokine levels that substantially increases the risk of multiple adverse health conditions including T2DM, hypertension, CVD, nephrotic syndrome, and even cancer [9].
The presence of Metabolic syndrome as per the WHO requires the presence of any one of DM, impaired fasting glucose or insulin resistance, impaired glucose tolerance and at least two of the following conditions: hypertension, central obesity, dyslipidaemia and high creatinine-albumin ratio.Consequently, the co-existence of the above three conditions (diabetes, hypertension and abdominal obesity) in an individual fulfils the diagnostic criteria for Metabolic Syndrome [10].
A recently published systematic review estimated 30% prevalence of Metabolic syndrome among the adult population in India with six times higher odds of the condition in obese individuals [11,12].Regardless of prior histories of cardiovascular events, people with Metabolic syndrome have an average four-fold increased risk of getting a stroke or myocardial infarction and a two-fold increased risk of dying from a comparable event [13].
Addressing the challenge of Metabolic syndrome in India is essential towards reducing the risk of NCD related complications with high morbidity, mortality, and associated socioeconomic health costs.Lifestyle modifications through healthy diet and exercise can reverse prediabetes, earlystage hypertension, and abdominal obesity thereby reducing the risk of its complications [14,15].Furthermore, in existing patients with DM and/or HTN with abdominal obesity, adherence to medications apart from healthy lifestyle and self-care is crucial for maintaining controlled blood glucose and reduced blood pressure levels that reduce the risk of complications [16,17].However, evidence from national level surveys from India suggest that most patients with DM and/or HTN fail to achieve optimal blood pressure and glycemic control that is associated with reduced quality of life and poor health outcomes [18,19].Patients with multimorbidity conditions as in Metabolic syndrome are subjected to complex pharmacological regimes that is associated with reduced medication adherence due to polypharmacy and regimen complexity and potential drug interactions and associated side effects [20,21].
Care cascade for a chronic disease indicates the sequential steps a person would take from the stages of screening, diagnosis, treatment initiation, and achievement of target health outcomes.Analysis of these cascade can help to generate quantitative evidence on the gaps in the existing framework for delivery of care and the areas of concern where quality of care warrant improvement [22].However, till date, evidence from nationally representative survey data has not been utilized to assess the quality and effectiveness of the care cascade especially in young and middle-aged patients with Metabolic syndrome in India.
We therefore conducted this study with the objective of ascertaining the burden, determinants, and care cascade in the young and middle-aged patients having co-existing HTN, DM, and abdominal obesity in India.

Data Source:
The study examined information from the National Family Health Survey (NFHS-5) conducted in India from 2019 to 2021.A two-stage stratified sample is utilized in the NFHS-5.The probability proportional to size (PPS) sampling method was used to select the primary sample units (PSUs), which were villages in rural areas and Census Enumeration Blocks (CEBs) in urban areas.This study analysed data from men and women aged 18-49 years who consented to blood pressure and random blood sugar measurements [8].

Sample size:
The study's sample size consisted of 788974 individuals aged 15-49 years (695707 women and 93267 men).

Outcome variables:
(1) Diabetes-hypertension comorbidity along with high waist circumference was the primary outcome variable of this study.Cases of DM and HTN included both previously diagnosed cases and newly diagnosed cases.

Independent variables:
Covariates included age, sex, employment status, educational attainment, smoking status, level of physical activity, and marital status (individuallevel variables) and wealth status, media access, place of residence, and region (household level variables).
(2) Physical Activity Levels: Information on physical activity was not directly available in the NFHS-5 dataset.Hence, occupation was considered as a surrogate to assess the physical activity levels.Any respondent whose work responsibilities involved physical activities were regarded as 'involved in an occupation with high physical activity'; otherwise, they were considered to 'involve less physical activity' i.e.,Not working, clerical and sales jobs = involve less physical activity and other job types = involve high physical activity [25].
(3) Diet: was categorized into a high and low-fat diet based on previous literature [26,27].The high-fat diet consisted of individuals who said 'Yes' to either "Daily eggs", "Daily fish", "Daily chicken or meat" or "Daily fried foods" consumption.Whereas, the remaining participants were put in the Low-fat diet category.
(4) Additional Comorbidities: This was treated as a dichotomous variable where respondents were assigned to the 'No comorbidity' group if they responded 'no' to all the following questions: do you currently have any heart disease?; do you currently have chronic respiratory diseases including asthma?; do you currently have a goitre or any other thyroid disorder?; do you currently have chronic kidney disease?If the participant responded 'yes' to any one or more of the questions above, then they were grouped in the "one or more comorbidity" group.
(5) Media Exposure: If the respondent said 'no' to the question: "Owns a mobile telephone" and said "not at all" to the question: "frequency of watching television/listening to the radio/ reading the newspaper" then the participant was considered to have "no media exposure".If the respondent said 'yes' to any of the questions mentioned above, then the participant was considered to "have media exposure".

Operational Definitions:
(1) Previously diagnosed patients with DM: Those who said yes to "told they had high glucose levels on two or more occasions by a doctor or other health professional", or taking medications to lower blood glucose levels were considered as previously diagnosed.
(2) Newly diagnosed patients with DM: Individuals who were not fasting and had Random Blood Sugar (RBS) levels ≥200 mg/dl or ≥126 mg/dl if fasting for ≥8 hours during the survey, and responded 'no' to the following two questions: 1. Told they had high glucose on two or more occasions by the doctor.
2. Currently taking prescribed medicine to lower glucose levels.
(3) Previously diagnosed patients with Hypertension: Those who said yes to "told they had high bp on two or more occasions by a doctor or other health professional", or taking medications to lower blood pressure were considered as previously diagnosed.
(4) Newly diagnosed patients with Hypertension: Individuals who had an average of the last two blood pressure readings (BP) ≥140/90 mmHg on screening during the survey and responded 'no' to the following two questions: 1. Told they had high BP on two or more occasions by the doctor.
2. Currently taking prescribed medicine to lower BP.
(5) Abdominal Obesity: Present if waist circumference ≥35 inches for women and ≥40 inches for men.
(6) On Diabetes Treatment: Individuals who responded 'yes' to the following question: "Currently taking a prescribed medicine to lower blood glucose", were considered to be on treatment for hypertension.(7) On Hypertension Treatment: Individuals who responded 'yes' to the following question: "Currently taking a prescribed medicine to lower blood pressure", were considered to be on treatment for diabetes.
(8) Full treatment was considered as the previously diagnosed cases of DM and HTN initiated on both anti-diabetes and antihypertensive treatment (9) Partial treatment was considered as the previously diagnosed cases of DM and HTN initiated on either anti-diabetes or antihypertensive treatment but not both.
(10) Metabolic syndrome was defined as per National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) [28] as the presence of three or more of the following five criteria: waist circumference over 40 inches (men), or 35 inches (women), blood pressure over 130/85 mmHg, fasting triglyceride levels (TG) over 150 mg/dl, fasting High-density lipoprotein (HDL) cholesterol level <40 mg/dl (men), or 50 mg/dl (women), and fasting blood sugar over 100 mg/dl.Since, data on TG and HDL was not available in the NFHS, we defined metabolic syndrome as the presence of the remaining 3 conditions.

Methodology:
For blood glucose testing, the Accu-Chek Performa glucometer with glucose test strips was used to collect finger-stick blood samples.A previously undiagnosed individual was considered to have diabetes if the RBS ≥200mg/dl.Blood pressure was measured for all women and men aged 15 and above using an Omron Blood Pressure Monitor to determine the prevalence of hypertension.Blood pressure measurements for each respondent were taken three times with an interval of five minutes between readings [8].The average of the second and third measurements was taken and participants with SBP of ≥140 mmHg and/or a DBP of ≥90 mmHg were regarded as hypertensive, while those already on antihypertensive medicines to regulate their BP were also considered hypertensive [23].
The waist circumference (WC) is a validated measurement of abdominal obesity [29].The waist circumference measurement for assessment of abdominal obesity were done by using Gulick tapes [8].

Statistical Analysis:
Categorical variables were reported as frequencies and proportions.Continuous variables were reported as means and standard deviations (SD).
Bivariate analysis was performed and the chi-square test was used to identify the relationship between dependent and predictor variables.Variables that were statistically significant in the bivariate analysis were put in the adjusted multivariable logistic regression model.The model assumptions regarding linearity in the logit function, multicollinearity, and the presence of outliers were assessed.Furthermore, to evaluate the treatment seeking behaviour of previously diagnosed DM-HTN comorbid patients having high waist circumference, the treatment behaviour was categorized into three groups: No treatment for both DM and HTN, partial treatment (i.e., treatment for either DM or HTN), and full treatment (for both DM and HTN).We applied multinomial regression model to estimate the regression coefficients for all three treatment behaviours.Variables found to be significantly associated in the unadjusted model were included in the adjusted multinomial model.
We utilized the modified Poisson regression approach [30] for assessing the determinants of previously diagnosed, incident and prevalent DM-HTN comorbid cases with high-waist circumference.The model was fit using a Generalized Linear Model (GLM) with the Poisson family and a robust error variance.Model fit was checked by Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC).A variable was considered to be statistically significant if the P-value was less than 0.05.The "svy" suffix was applied to perform weighted analysis to regulate the clustering effect.Data analysis was conducted using Stata version 15.1 (StataCorp, College Station, TX, USA).

Ethics approval:
The ethical approval for NFHS 5 survey was obtained from ethics review board of the International Institute of Population Sciences, Mumbai, India.Written and informed consent was obtained from each respondent before participating in the survey, additionally, written informed consent was obtained from the parent/guardian of each respondent under 18 years of age.No separate ethical approval was required for this secondary data analysis, since the NFHS-5 dataset is an anonymous publicly available dataset with no identifiable information about the study participants.The data were accessed on the 15 th of February 2023 for research purposes, and authors never had access to information that could identify individual participants during or after data collection.
Table 1 reports the socio-demographic and lifestyle characteristics among the participants having DM-HTN comorbidity with high waist circumference.Among the previously diagnosed cases, a majority of them were middle-aged (41-49 years) (59.12%) and females (96.18%).
Among the previously diagnosed cases of DM-HTN comorbidity with high waist circumference, 46.16% (95% CI: 43.02 to 49.32) cases were treated with both anti-diabetes and antihypertensive medication (full treatment), 19.14% (95% CI: 17.12 to 21.33) cases were on either antidiabetes or antihypertensive medication but not both (partial treatment), while 34.71% (95% CI: 31.70 to 37.84) cases were on neither treatment (untreated).Table 2 reports the treatment seeking behaviour of previously diagnosed DM-HTN comorbid patients having high waist circumference.
Upon unadjusted multinomial regression analysis, males and increasing age were significantly associated with the odds of availing partial or full treatment for DM-HTN comorbidity.Similarly, higher wealth index, urban residency, increasing BMI, exposure to media and presence of additional comorbidities were positively associated with availing full treatment as compared to availing no treatment.Adjusted analysis showed that individuals belonging to age group 41-49 years (aRRR = 3.19, 95% CI: 1.96 to 5.20) and richest wealth index (aRRR = 2.81, 95% CI: 1.36 to 5.81) were more likely to be on partial treatment rather than not taking any treatment.Similarly, individuals having age 41-49 years (aRRR = 18.03, 95% CI: 9.87 to 32.94), richest wealth index (aRRR = 2.42, 95% CI: 1.14 to 5.11), urban residency (aRRR = 1.62, 95% CI: 1.15 to 2.27), obesity (aRRR = 1.56, 95% CI: 1.02 to 2.37), media exposure (aRRR = 1.52, 95% CI: 1.03 to 2.55) and additional comorbidities (aRRR = 1.60, 95% CI: 1.16 to 2.22) were more likely to be on full treatment as compared to not being on either treatment.Further, females (aRRR = 0.42, 95% CI: 0.20 to 0.87) were less likely to be on full treatment than no treatment as compared to males.Table 3 reports the association of the socio-demographic and lifestyle characteristics among both the cases of DM-HTN comorbidity with highwaist circumference stratified by their time of diagnosis (previous, new, total).On adjusted analysis, increasing age, female sex, higher wealth index, increasing BMI and exposure to media had significantly higher odds of having a previous diagnosis of DM-HTN comorbidity with highwaist circumference.Similarly, increasing age, lower education levels, urban residence, higher wealth index and high BMI were the predictors associated with newly diagnosed cases of DM-HTN comorbidity with high-waist circumference.The risk factors that were significantly associated with occurrence of DM-HTN-comorbidity with high waist circumference in the total cases (both previously diagnosed and new cases) were the middle age group (41-49 years) compared to younger aged cases (aRR = 6.12, 95% CI: 5.24 to 7.15), females compared to male cases (aRR = 1.62, 95% CI: 1.25 to 2.10), higher compared to no education (aRR = 0.84, 95% CI: 0.71 to 0.99), cases belonging to richest wealth index compared to lower wealth quintiles (aRR = 1.91, 95% CI: 1.52 to 2.40), obesity (aRR = 4.68, 95% CI: 4.06 to 5.40), high fat diet compared to low fat diet (aRR = 1.18, 95% CI: 1.06 to 1.30) and presence of additional comorbidities compared to no other self-reported comorbidities (aRR = 1.47, 95% CI: 1.32 to 1.63).Furthermore, less than half (46.83%) of the cases with DM-HTN comorbidity with high waist circumference had both controlled BP (<140/90) and blood glucose levels (RBS<180).However, nearly 18% of the cases had both suboptimal blood pressure and glycemic control (Figure 1).Regional variation was observed in the prevalence of DM-HTN comorbidity with high waist circumference across Indian states and union territories with Chandigarh having the highest prevalence (2.53%), followed by Tamil Nadu (2.31%), while the lowest was observed in Meghalaya (0.12%) (Figure 2).

DISCUSSION
The present study observed the prevalence of DM-HTN comorbidity with high waist circumference equivalent to metabolic syndrome (Metabolic syndrome) was lower (0.75%) compared to regional estimates of metabolic syndrome [31,32] although it is an underestimation as the case definitions in this study did not account for elevated triglyceride or HDL-C levels which were unavailable, and also the lack of older adults and elderly in the sample.
The overall prevalence of DM-HTN comorbidity with high waist circumference was significantly higher in females, a finding consistent with the findings of a meta-analysis of studies from India.[11].The presence of Metabolic syndrome in this study was also associated with increasing age and higher BMI, findings that are consistent with the global evidence [33][34][35].Furthermore, in this study, people living in urban areas were 1.2 times more likely to have Metabolic syndrome as compared to rural residents suggestive of the linkage of adverse social determinants such as sedentary lifestyle, dietary changes and also stress in urban areas [33].
The present study findings indicate that higher education levels decrease the risk of having undiagnosed metabolic syndrome in accordance with a study conducted in China [36], suggestive of the impact of adverse social determinants of health contributed to delayed screening and diagnosis of DM and HTN in individuals with lower educational status compared with their counterparts.Less than half of the cases in our sample (46.8%) having DM-HTN comorbidity with high waist circumference and previously initiated on treatment had poorly controlled blood pressure and blood glucose levels that may reflect either poor medical adherence, or poor response to hypertension treatment [37] and insulin resistance [38].Furthermore, patients with Metabolic syndrome satisfying criteria of having high waist circumference, elevated blood pressure and triglyceride levels require early and effective treatment to prevent the onset and progression of cardiovascular complication [39].However, in this study, nearly one in two cases with Metabolic syndrome were undiagnosed that were detected on survey-based screening of blood pressure and blood glucose levels signifying an iceberg phenomenon of disease wherein only a fraction of the total cases is clinically diagnosed and initiated on effective treatment.Consequently, public health strategies to control the pandemic of Metabolic syndrome driven cardiovascular disease burden in the developing world including India requires scaling up of screening individuals above age 30 especially those with any high-risk factor for Metabolic syndrome for HTN, DM, abdominal obesity, and elevated blood triglyceride levels.Furthermore, initiation of effective treatment for cases diagnosis with HTN, DM, or Metabolic syndrome is of paramount significance.In this context, the revamped national program for noncommunicable diseases (NP-NCD 2023-2030) in India has set an ambitious 75:25 initiative for placing 75 million patients with HTN or DM on standard by 2025 [40].
The study has certain strengths including its analysis of a large sample size and nationally representative dataset with adequate geographical diversity that supports generalizability of the findings.However, there are also some major study limitations.First, the cross-sectional design of the study does not permit assessment of temporal association and precludes causal assessment.Second, information for two important components of metabolic syndrome, serum cholesterol and triglyceride levels were not available in the NFHS datasets that is likely to have contributed to significant underestimation of the burden of the problem.Third, there may be some recall bias, although blood pressure and random blood sugar measurements were conducted as part of the study.However, the lack of fasting blood glucose and glycated haemoglobin measurements precluded the validated estimation of glycemic control in the patients.Lastly, no direct information on physical activity was available in the datasets so a surrogate was obtained from the individual's occupation which may not accurately reflect the physical activity status of the participants.
In conclusion, nearly 6 in 10 young and middle aged-population in India with DM-HTN-abdominal obesity triad are not initiated on treatment for DM and HTN comorbidities especially those from socioeconomically disadvantaged groups, while a majority of the previously diagnosed cases have uncontrolled blood pressure and poor glycemic control.The poor cascade of care for DM and HTN in these high-risk group of patients may substantially increase their risk for early progression and severity of microvascular and macrovascular complications especially cardiovascular disease.Early diagnosis of cases of metabolic syndrome including DM and HTN, with early initiation of effective medication and treatment, regular monitoring and targeted reduction of blood pressure, blood glucose, and body weight through primary health system strengthening and community engagement remain the cornerstone of reducing complications from these debilitating health conditions.

Conflicts of interest = None
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TABLES Table 1 :
Socio-demographic and lifestyle characteristics of DM-HTN comorbid individuals with high waist

Table 3 : Factors associated with DM-HTN-abdominal obesity among high-risk young and middle-aged individuals*
Rate Ratio; aRR, Adjusted Rate Ratio; CI, Confidence Interval; Ref, Reference Category; DM, Diabetes Mellitus; HTN, Hypertension; BMI, Body Mass Index * P < 0.05, ** P < 0.001 a Denominator (n = 267517) taken as individuals with higher-risk of metabolic syndrome, i.e., detected with DM or HTN or high waist or high BMI (≥25.0)